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Abstract

BACKGROUND: Severe sepsis is frequently complicated by organ failure and accompanied by high mortality. Patients surviving severe sepsis can have impaired health-related quality of life (HRQOL). The time course of changes in HRQOL in severe sepsis survivors after discharge from the intensive care unit (ICU) and during a general ward stay have not been studied.

METHODS: We performed a long-term prospective study in a medical-surgical ICU. Patients with severe sepsis (n = 170) admitted for >48 h were included in the study. We used the Short-form 36 to evaluate the HRQOL of severe sepsis patients before ICU and hospital stay and at 3 and 6 mo after ICU discharge. Furthermore, we compared the results for ICU admission and 6 mo after ICU discharge with those of an age-matched general Dutch population.

RESULTS: At 6 mo after ICU discharge, 95 patients could be evaluated (eight patients were lost to follow-up, 67 died). HRQOL showed a multidimensional decline during the ICU stay and gradual improvement over the 6 mo after ICU discharge for the social functioning, vitality, role-emotional, and mental health dimensions. However, 6 mo after ICU discharge, scores for the physical functioning, role-physical, and general health dimensions were still significantly lower than preadmission values. Physical and Mental Component Scores changed significantly over time. In particular, the Mental Component Score showed a small decline at ICU discharge but recovered rapidly, and at 6 mo after ICU discharge had improved to near normal values. In addition, Short-form 36 scores were lower than those in a matched general population in six of the eight dimensions, with the exception of social functioning and bodily pain. Interestingly, the preadmission HRQOL in surviving patients was already lower in three of the eight dimensions (role-physical, mental health, and vitality) when compared with the general population.

CONCLUSIONS: Severe sepsis patients demonstrate a sharp decline of HRQOL during ICU stay and a gradual improvement during the 6 mo after ICU discharge. Recovery begins after ICU discharge to the general ward. Nevertheless, recovery is incomplete in the physical functioning, role-physical, and general health dimensions at 6 mo after ICU discharge compared with preadmission status.

Severe sepsis is frequently complicated by organ failure, which accounts for the persisting high mortality rate.1,2 Although survival is a primary goal of treatment in the intensive care unit (ICU), health-related quality of life (HRQOL) after discharge is an important issue for patients, relatives, and the physicians and nurses involved in the patient's treatment. Patients surviving severe sepsis may have impaired quality of life similar to that of survivors of adult respiratory distress syndrome (ARDS).3 HRQOL is a complex outcome measure that can be measured using a generic instrument such as the Short-form 36 (SF-36). Heyland et al.4 showed that estimation of HRQOL with the SF-36 in ICU patients is possible and reliable. In particular, estimating patients' preadmission HRQOL with the SF-36 seems to be a valid approach, although proxies must frequently complete the questionnaire.5,6 Assessment of HRQOL can improve the answers given by doctors and nurses to patients and relatives about the patient's prospects.7,8

The purpose of this study was twofold: first, to describe the impact on HRQOL in patients with severe sepsis during the ICU and hospital stay, and until 6 mo after ICU discharge, using the SF-36; and second, to compare HRQOL on admission and at 6 mo after ICU discharge in survivors of severe sepsis with HRQOL in the general Dutch population.

METHODS

This study is part of a larger project aimed at the evaluation of HRQOL in critically ill patients. Patients eligible for this study were those admitted to the 10-bed closed-format mixed surgical-medical ICU of the Gelre Lukas hospital, a 654-bed university-affiliated teaching hospital in Apeldoorn, The Netherlands. Between September 2000 and April 2004, all admissions were screened for study participation. Patients admitted for the first time to the ICU with an expected length of stay for more than 48 h and fulfilling the criteria for severe sepsis were eligible for inclusion. The study was approved by the local ethics committee. Informed consent was given by proxies and later by patients before answering the HRQOL questionnaire. Patients with an impaired level of self-awareness or without the ability to communicate adequately at any time during the study were excluded.

Severe sepsis was defined by the presence of infection or a likely focus of infection, two or more systemic inflammatory response syndrome criteria, and dysfunction of one or more organ systems. Organ dysfunction was defined according to previously published criteria by Bone et al.9 Patients' demographic data and severity of illness (Acute Physiology and Chronic Health Evaluation, APACHE II) were also collected.

Health-Related Quality of Life

The SF-36 version 1 (copyright 1993, Medical Outcome Trust), a generic, widely used standardized health status questionnaire, was used to measure HRQOL. This measurement contains eight multi-item dimensions: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Answers to the 36 items were transformed and weighed according to earlier recommendations, and subsequent scoring was performed according to predefined guidelines.10 Higher scores represent better functioning, with a range from 0 to 100. Furthermore, scores were aggregated to summary measures representing a Physical Component Score (PCS, mainly reflecting physical functioning, physical role, pain, and general health) and a Mental Component Score (MCS, mainly reflecting vitality, social functioning, emotional role, and mental health).11 Population scores on PCS and MCS have been standardized at 50 (SD10 representing 1).11 The SF-36 has been validated in primary care, for members of the general population12,13 and for assessing quality of life after critical illness.4,14 Translation, validation, and norming of the Dutch-language version of the SF-36 health questionnaire were evaluated in 1998 in community and chronic disease populations.15

We assessed the effects of critical illness and ICU treatment on HRQOL by using the SF-36 at admission (proxies), ICU discharge (patients), hospital discharge (patients), and at 3 and 6 mo after ICU discharge (patients). This evaluation period was predefined, as earlier studies indicated that the changes are minimal among ICU patients after this period.16,17

As most ICU patients are not able to complete a questionnaire at the time of admission, proxies must be frequently used. In this study, we assessed HRQOL in the 4 wk before admission through proxies. This approach was validated in an earlier study by our group.5 Proxies had to be in close contact with the patient on a regular basis.

The first SF-36 questionnaire was completed within 48 h of admission. At the time of discharge from the ICU and the hospital, the patients were specifically asked to score their HRQOL according to their current situation instead of their HRQOL 4 wk before (the time frame of the SF-36). During hospital admission, patients completed the questionnaire by personal interview. All interviews were performed by the same investigator (J.H.).

After discharge from the hospital, the questionnaire was completed by personal interview or taken by phone. When needed, the investigator (J.H.) visited the patients at home. The average time required to complete the questionnaire was 15–20 min.

Presence or absence of delirium in the patients, especially at ICU and hospital discharge, was based on the opinions of the nurses, doctors involved in daily care of the patients, and close relatives. Patients suspected of delirious states or other incapacities were excluded from the study.

Statistical Analysis

Paired t-tests were used for evaluating changes between two time points. To analyze individual changes over time, a MANOVA test was used, with Wilks' lambda as the multivariate test and Bonferroni correction as the adjustment for multiple comparisons, as we had more than one dependent variable with repeated measures. We studied APACHE II score and age by using them as covariates in multivariate analysis of covariance. SF-36 dimensions of survivors were compared with normative data from the age-matched Dutch general population,15 using a one-sample t-test. To examine the relative magnitude of changes over time and between groups, effect sizes were used based on the mean change found in a variable divided by the baseline standard deviation.18 Effect sizes estimate whether particular changes in health status are relevant. Following Cohen,19 effect sizes of ≥0.20, ≥0.50, and >0.80 were considered small, medium, and large changes, respectively. Data were analyzed using the Statistical Package for the Social Sciences (version 11.5). All data are expressed as means ± sd where appropriate, unless otherwise indicated. P < 0.05 was considered to be statistically significant.

RESULTS

Demographic and Clinical Characteristics

A baseline HRQOL was obtained from all 170 patients (63.5% men, 36.5% women) with severe sepsis. HRQOL was also measured at ICU discharge (n = 121), at hospital discharge (n = 101), and at 3 (n = 96) and 6 mo (n = 95) after ICU discharge. The mean age was 68 ± 12 yr. At 6 mo, 67 severe sepsis patients had died (38.3%) and eight patients were lost to follow-up (Fig. 1). The most frequent origins of severe sepsis were the abdomen (47.1%) and respiratory tract (35.5%). The type of admission was predominantly medical (58.2%) or acute surgery (35.9%). Demographic and clinical characteristics of study patients are shown in Table 1.

Changes of HRQOL Over Time in Survivors

During the study period, a decrease was found in the physical functioning, role-physical, general health, vitality, and social functioning dimensions. Scores were lower at ICU discharge and hospital discharge in comparison with baseline values (Table 2). These HRQOL aspects improved at 3 and 6 mo after ICU discharge. There was a distinct pattern of a sharp multidimensional decline during ICU stay and gradual improvement in the 6 mo after ICU discharge in all dimensions except for bodily pain and the MCS. Nevertheless, 6 mo after ICU discharge (n = 95), average scores for the physical functioning, role-physical, and general health dimensions were still significantly lower than baseline values (all P < 0.05; Table 2; Fig. 2). Effect size was medium for the role-physical (0.51) dimension and small for the physical functioning (0.37) and general health (0.41) dimensions. Bodily pain did not change at all during the study period. HRQOL decreased significantly over time in all dimensions in severe sepsis survivors except bodily pain (P < 0.05; Table 2). Interestingly, the significant difference of the bodily pain dimension in sepsis survivors was based on a higher mean at 6 mo compared with preadmission (P < 0.002). The PCS (P < 0.001) and MCS (P < 0.05) changed significantly over time (Fig. 3). The MCS showed a small but significant decline from ICU admission and had recovered to pre-ICU admission values at hospital discharge and improved even further by 6 mo after ICU discharge (Table 2). These changes over time were not influenced by age or admission APACHE II score.

Comparison at 6 mo: Severe Sepsis Survivors Versus General Population

Patients who survived severe sepsis up to 6 mo were compared with an age-matched general population. The average SF-36 scores were lower than normal (i.e., worse) in six of the eight dimensions studied (all P < 0.01), the exceptions being the social functioning and bodily pain dimensions (Table 2). Effect size was medium for the physical functioning, role-physical, and general health dimensions (range: 0.50–0.73). Average SF-36 scores of the bodily pain dimension were higher in the severe sepsis survivors, indicating less pain (Fig. 2, Table 2).

Comparison of HRQOL Before ICU Admission with HRQOL in the General Population

The preadmission HRQOL of severe sepsis survivors was compared with HRQOL in the general population. Three of the eight dimension scores (role-physical, mental health, and vitality) were lower (i.e., worse) in the severe sepsis survivors (all P < 0.001). However, effect sizes tended to be small (range: 0.13–0.28) (Table 3).

DISCUSSION

This is the first long-term study evaluating the time course of changes in HRQOL for sepsis survivors at ICU admission and discharge, after a general ward stay, and at 6 mo after ICU discharge. Severe sepsis was associated with a sharp multidimensional decrease of HRQOL during the ICU stay and gradual improvement in the 6 mo thereafter. These changes over time were not influenced by age or APACHE II score on admission, which was also reported by others.20 Interestingly, the bodily pain dimension did not change at all during our study. A possible explanation for a lack of change may be a phenomenon called “response shift,” i.e., a change in self-evaluation resulting from changes in internal standards or values in patients confronted with a life-threatening disease or chronic incurable disease.21 One could argue that response shift is more likely to occur in those dimensions which are prone to subjective influences such as pain. However, other studies in general ICU patients22 and in ARDS patients23 showed that the bodily pain dimension scores at 3 and 6 mo after discharge were decreased.

The observed temporal decrease in HRQOL during critical illness, with gradual improvement over time, concurs with previous findings.7,24 Graf et al.7 used the SF-36 in medical ICU patients staying for >24 h and found that physical and role-emotional scores had deteriorated 1 mo after ICU discharge, but returned to baseline 9 mo thereafter. In addition, they showed that the Mental Summary Scale did not change during the investigational period. Wehler et al. investigated patients with multiple organ dysfunction syndrome (MODS) and found that 83%–90% of the survivors had regained HRQOL at 6 mo after ICU discharge, although persistent deterioration was especially noted in the physical health domains.23,25 Herridge et al.23 found that patients with ARDS have persistent functional limitation 1 yr after being discharged from the ICU. In line with our findings, the latter studies showed no impact on mental health domains.23,25

Our study showed a temporal decrease in most domains of HRQOL during ICU stay which was followed by recovery starting immediately after ICU discharge. Other investigators have demonstrated persisting disturbance in HRQOL after ICU stay. Using a different scoring method, the EQ-5D, a study in sepsis survivors (not evaluating baseline values) showed that HRQOL of sepsis survivors was fair at 6 mo after ICU discharge. Nevertheless, moderate to severe problems were reported at percentages ranging from 24% to 46% in the five dimensions of the EQ-5D, which was similar to the HRQOL of other critically ill survivors admitted without sepsis.26 Moreover, the significantly lower response rate for the sepsis group could have induced a response bias, whereby survivors from the sepsis group with a lower HRQOL may be under-represented.26 In addition, using the EQ-5D, in predominantly abdominal sepsis, no significant difference in HRQOL was found between sepsis and trauma patients 2 yr after intensive care treatment. HRQOL was reduced to the same level; i.e., 82% of the patients reported a problem (moderate or extreme) in at least one dimension, but most patients (74%) reported no problems in self-care.27 Bosscha et al.28 determined HRQOL after severe bacterial peritonitis at least 1 yr after discharge and found that about 75% of patients regained a good HRQOL, although some patients, especially those who suffered from persistent polyneuropathy and mental disorders, showed persistent limitations in daily life. Another study in abdominal sepsis patients 15 mo after ICU discharge showed that 75% of survivors were independent, ambulatory, and capable of self-care.29 None of the survivors became completely disabled.

However, in addition to the published literature, our study has shown that, in severe sepsis survivors, recovery already starts after discharge from the ICU to the general ward. In the critical care environment, nursing care can have a positive effect on the psychological well-being of patients and relatives.30 In particular, the way doctors and nurses support the patient during critical illness and recovery periods is seen as an important factor in the patients' contentedness and perceived HRQOL after ICU discharge.31

Comparison of General Population with Sepsis Patients at ICU Admission

The preadmission HRQOL in our study of severe sepsis survivors showed that three of the eight dimension scores (role-physical, mental health, and vitality) were already lower in the severe sepsis survivors compared with HRQOL in the general population. This concurs with the finding that HRQOL at admission was reduced in comparison with a matched population of patients with MODS,25 but also in comparison with general ICU patients.7 In contrast to these findings, pre-ICU HRQOL was reported to be unimpaired in 70% of medical-surgical ICU admissions.32 These differences may be explained by differences in the way HRQOL was measured, but also by the geographical setting, with inherent differences in case mix. Nevertheless, the aforementioned data indicate that severe sepsis patients frequently have a lower HRQOL before critical illness occurs.

Comparison of General Population with Sepsis Patients 6 mo After ICU Discharge

Six months after ICU discharge, HRQOL in severe sepsis survivors was still lower compared with a general population. This impairment occurred particularly in the role-physical, general health, and physical functioning dimensions. Heyland et al.4 also found that survivors of sepsis have significantly lower average scores in physical functioning and general health dimensions, but exhibit no differences in the emotional component compared with the general population. A limitation of that study is the small sample of included patients (n = 30), which also puts the study of Perl et al. in a different perspective. Perl et al.33 assessed the HRQOL of 38 patients who survived Gram-negative sepsis and found that septic patients scored poorly on domains within the SF-36 that measure perceived physical function when compared with the general population. Even stronger impairment in HRQOL was reported by Pettila et al.,34 who studied patients with MODS using the SF-36. They compared HRQOL 1 yr after ICU treatment with HRQOL in a general population and reported impaired scores for ICU survivors in all eight domains. On balance, it would seem that severe sepsis survivors have reduced HRQOL, especially pertaining to physical health. Whether this outcome is a result of the severe sepsis or the underlying co-morbid illness is unknown.

Strengths and Limitations

We conducted a long-term, prospective study which measured HRQOL not only before and after hospital discharge, but also at ICU discharge and in a 6-mo period after ICU discharge. It is possible that the follow-up time of 6 mo may be too short to evaluate final improvement in HRQOL in sepsis patients. However, this evaluation period of 6 mo was predefined in view of some earlier studies that indicated that further changes are minimal among ICU patients after this period.7,16

Only patients on their first admission and admitted for more than 48 h to the ICU were included. Therefore, these results are not generalizable to the group of patients with a short ICU stay or with lower disease severity. Another limitation could be that we did not make a distinction between severe sepsis and septic shock.

It is also important to measure HRQOL before and after ICU discharge to examine the impact of the critical illness and ICU admission on HRQOL. On admission to the ICU, the emergency procedures and abnormal levels of consciousness limit the assessment of HRQOL by the patient. We chose to use proxies for preadmission scores, instead of a retrospective assessment at ICU discharge,35 because the critical illness can influence the patients' recollection of their previous health. The approach of using proxies in this setting was validated in an earlier study by our group5 and by other studies.6,35 However, some investigators have raised concerns about proxy estimations of HRQOL in populations with high disease severity.36 The same study suggested that predictions of poor ICU outcome may be exaggerated if proxies underestimate HRQOL.36 However, in contrast to the situation in our previous validation study, where patients and their proxies were interviewed within 72 h of ICU admission, those investigators interviewed patients 3 mo after ICU discharge and their proxies at study entry. This makes it entirely possible that survivors of critical illness may overestimate preadmission HRQOL.

In our study, at the time of ICU and hospital discharge, the patients were specifically asked to score their HRQOL according to their current situation instead of their HRQOL 4 wk before admission. This was necessary to avoid overlap between periods, but complicates the interpretation of the results at ICU discharge and hospital discharge. However, in our opinion, this is a reasonable approach to gain insight into the patients' perceptions of their HRQOL at that time. Still, a direct comparison of different time points is hampered by the different recall periods and the use of both proxies and patients.

In addition, the presence of delirium could have influenced the response, although we made an effort to screen out delirious patients.

Another limitation may be the phenomenon of response shift, mentioned earlier. Social functioning, for instance, could be perceived differently in the clinical setting because of the many visitors in the hospital and postcards received. Although we did not measure response shift in the present study, dimension scores for bodily pain, social functioning, and mental health at ICU and hospital discharge were higher than we expected. Future research should evaluate whether these effects are at least in part caused by response shift.

CONCLUSION

This study indicates that HRQOL in severe sepsis survivors showed a sharp multidimensional decline during ICU stay and a gradual improvement approaching normal values 6 mo after ICU discharge, with recovery already beginning after discharge from the ICU to the general ward. This implies that intensive care treatment of severe sepsis is worthwhile. However, despite survival, patients report incomplete recovery in the physical functioning, role-physical, and general health dimensions at 6 mo after ICU discharge, compared with the situation before their ICU stay. A follow-up clinic for patients after ICU and hospital discharge could be a way of improving the speed and quality of long-term recovery from severe sepsis.

26. Granja C, Dias C, Costa-Pereira A, Sarmento A. Quality of life of survivors from severe sepsis and septic shock may be similar to that of others who survive critical illness. Crit Care 2004;8:R91–R98

Revista Panamericana De Salud Publica-Pan American Journal of Public HealthAnalysis of quality of life following hospital discharge among survivors of severe sepsis and septic shockWestphal, GA; Vieira, KD; Orzechowski, R; Kaefer, KM; Zaclikevis, VR; Mastroeni, MFRevista Panamericana De Salud Publica-Pan American Journal of Public Health, 31(6):
499-505.

Journal of Emergency NursingImplementation of Early Goal-Directed Therapy for Septic Patients in the Emergency Department: A Review of the LiteratureTuri, SK; Von Ah, DJournal of Emergency Nursing, 39(1):
13-19.10.1016/j.jen.2011.06.006CrossRef

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